statistical parametric mapping (spm) 2008 · in spm resampling can be postponed and the estimated...
TRANSCRIPT
Statistical Parametric Mapping (SPM) 2008
Finn Arup Nielsen
Lundbeck Foundation Center for Integrated Molecular Brain Imaging
at
Informatics and Mathematical Modelling
Technical University of Denmark
and
Neurobiology Research Unit,
Copenhagen University Hospital Rigshospitalet
February 8, 2008
Statistical Parametric Mapping (SPM) 2008
What is SPM?
0 5 10 15 20 25 30 35
SPM97d/SPM99
SPM99b
SPM99d
Stimulate
BRAINS
In−house
MRIcro
SPM97d
SPM97
AFNI
SPM
AIR
SPM95
SPM99
SPM96
Absolute frequency
Analysis software of first experiment in paper (top of list)
Figure 1: Histogram of used analysis softwareas recorded in the Brede Database, see ori-ginal at http://hendrix.imm.dtu.dk/services/jerne/-brede/index bib stat.html
A method for processing and ana-
lysis of neuroimages.
A method for voxel-based analysis
of neuroimages using a ‘general lin-
ear model’.
The summary images (i.e., result
images) from an analysis: Statisti-
cal parametric maps.
A Matlab program for processing
and analysis of functional neuroim-
ages — and molecular neuroimages.
SPM is very dominating in func-
tional neuroimaging
Finn Arup Nielsen 1 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
SPM — the program
Figure 2: Image by Mark Schram Christensen.
Image registration, seg-
mentation, smoothing, al-
gebraic operations
Analysis with general lin-
ear model, random field
theory, dynamic causal
modeling
Visualization
Email list with ∼ 2000
subscribers
Finn Arup Nielsen 2 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Data transformations
1 2 3 4 5 6 7 8
2
4
6
8
10
12
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
−3−2
−10
12
3
−3
−2
−1
0
1
2
30
0.2
0.4
0.6
0.8
1
Template
Image data
Realignment Smoothing General linear
Spatial
Normalization
Model
InferenceStatistical
Kernel Design matrix Statistical parametric map
Gaussian random fieldFalse discovery rateMaximum statistics permutation
Finn Arup Nielsen 3 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Image registration
Figure 3: Main window of SPM2. Image registrationare the three left upmost buttons.
Image registration: Move and warp
brain
Motion realignment of consecutive
scans (‘realign’). Within subject
Coregistration or intermodality reg-
istration, e.g., to registation a PET
and an MRI. Wihtin subject.
Spatial normalization: Deform brain
to a template. ‘MNI’ Templates are
distributed with SPM. Between sub-
jects.
Finn Arup Nielsen 4 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Realignment
Several images in the same modality from the same subject
Two-stage procedure:
1. Estimate movement. SPM: ‘Determine parameters’
2. Resample images based on estimated movement
In SPM resampling can be postponed and the estimated movement saved
in a .mat file with the ‘transformation matrix’.
Finn Arup Nielsen 5 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Coregistration
(a) PET template from SPM. (b) MRI T1 template from SPM.
Figure 4: The areas with the highest values in two modalities of PET and MRI brain scans: For registrationthe problem is that they are different!
Finn Arup Nielsen 6 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Spatial normalization
Figure 5: Warp of right subject to left subjects brain. Result in the middle. Image by Ulrik Kjems usingMRIwarp (Kjems et al., 1999a; Kjems et al., 1999b).
Finn Arup Nielsen 7 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Spatial normalization in SPM
Two-stage procedure:
1. Determine warp parameters by matching a subjects anatomical MRI
(‘Source image’) to a template (‘Determine parameters’).
These parameters are stored in a file with the postfix sn.mat
2. Apply (‘Write normalised’) the warp parameter to warp the anatomical
(T1 MRI) and the functional image (fMRI or PET) (‘Images to write’)
The new files have the prefix ‘w’ for warp.
By default SPM is normalizing to so-called ‘MNI-space’ which is slightly
different from the original ‘Talairach atlas’ (Talairach and Tournoux,
1988; Brett, 1999a; Lancaster et al., 2007).
Finn Arup Nielsen 8 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
. . . Spatial normalization in SPM
Warping may not work properly: Check the result, e.g., with ‘Check Reg.’
button in SPM.
There are a number of hidden parameters in SPM: smoothing, regular-
ization, ‘cutoff’ (how many basis functions), interpolation, bounding box,
etc.
‘[. . . ] if your normalized images appear distorted, then it may be
an idea to increase the amount of regularization’ (spm normalise ui.m)
If adjusting these parameters does work try to skull strip the volumes.
Finn Arup Nielsen 9 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Spatial smoothing
(a) Unsmoothed original. (b) Smoothed. FWHM=10mm.
Figure 6: T1 single subject template from SPM99.
Finn Arup Nielsen 10 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Spatial smoothing
−5 0 5 10 15 20 250
5
10
15
20
25
Fre
quen
cy
FWHM spatial filter width [mm]
Figure 7: Histogram of smoothing widthin the Brede database, see original athttp://hendrix.imm.dtu.dk/services/jerne/-brede/index bib stat.html
Accounts for anatomical variability.
Might increase signal to noise ratio.
Increase validity of SPM inference
Usually performed with with an
Gaussian kernel.
SPM command line
spm smooth(filenameIn, filenameOut, 16);
Here 16 is the ‘full width half max-
imum’ in millimeters
FWHM =√
8 ln2 σ ≈ 2.35σ.
An ‘s’ is prefixed on the filename.
Finn Arup Nielsen 11 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Spatial masks
Spatial mask: Exclude voxels from the statistical analysis, e.g., non-brain
voxels and brain voxels not (likely) ‘significant’.
SPM terminology
• Threshold, ‘absolute’, ‘relative’ (‘Grey matter threshold’).
• ‘Implicit mask’: Omit voxels that are zero or NaN.
• ‘Explicit mask’: A volume file specifying the which voxels to include
(ones and zeros).
• So-called ‘F-masking’ appeared in early versions of SPM: SPM94/5/6.
Finn Arup Nielsen 12 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Spatial mask — Global mean
0 50 100 150 200 250 300 350 400 4500
1000
2000
3000
4000
5000
6000
7000
8000
Voxel values
Fre
quen
cy
HistogramOrdinarySPM−typeOrdinary/8
Figure 8: Example of a histogram from a PET vol-ume (Noll et al., 1996).
What is the mean value of a brain
scan?
A simple mean will be affected by
the number of non-brain voxels.
These are around zero.
A more robust ‘global mean’
can be calculated in two-stages:
First the ordinary mean is com-
puted, then the mean of values
above mean/8. (Computed in
spm global.m and spm global.c avail-
able at SPM.xGX.rg)
The value is used for confounds and
masking operations.
Finn Arup Nielsen 13 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Noll’s PET motor SPM masking example
Figure 9: PET motor, left hand finger oppositiontask, 12 scans: Odd activation, even baseline (Nollet al., 1996). Red is without mask. Yellow withmask. Thresholded at t = 2.76 (P < 0.01).
SPM analysis: two-sample test, ‘no
grand mean scaling’, ‘omit global
calculation’.
‘Single-subject: conditions & co-
variates’, 0 covariates and nuisances
‘no global normalization’, ‘no grand
mean scaling’, mask (fullmean/8
mask).
Without a mask many non-brain
voxels appear with high statistics.
Finn Arup Nielsen 14 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Analysis with the general linear model
• The general linear model has the form (Mardia et al., 1979, eq. 6.1.1)
Y = XB + U,
where Y(scans×voxels) is the image data, X(scans×design variables)
is the ‘design matrix’ and B(design variables × voxels) contains para-
meters to be estimated and tested. The residuals U are usually as-
sumed Gaussian.
• Encapsulates many statistical models: t-test (paired, un-paired), F -
test, ANOVA (one-way, two-way, main effect, factorial), MANOVA,
ANCOVA, MANCOVA, simple regression, linear regression, multiple
regression, multivariate regression, . . .
• Widely used in functional neuroimaging through the SPM program
where it is performed in a mass-univerate setting — in parallel over
the columns of Y (Friston et al., 1995).
Finn Arup Nielsen 15 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Process for analysis
Specify design - Estimate - Test
Specify design: Set up the design matrix X
Estimate: Find the parameters B and the residuals U
Test: Specify a test (a ‘contrast’) and test-statistic threshold and view
the results.
Finn Arup Nielsen 16 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Basic models
Figure 10: SPM 2 main interface window with ‘Basicmodels’ button high lighted.
‘Basic models’ of SPM:
One-sample t-test, two-sample t-
test, paired t-test, one-way ANOVA,
one-way ANOVA with constant,
one-way ANOVA ‘within-subjects’,
simple regression (correlation), mul-
tiple regression, multiple regression
with constant, ANCOVA.
The models only vary because of
difference in specification of the de-
sign matrix.
Finn Arup Nielsen 17 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Simple regression
−1 0 1 2 3 4 5 6 7 8 9
0
2
4
6
8
10
12
14
16
18
y1
x1
u1
y2
x2
u2
y3
x3
u3
Figure 11: Simple regression.
In simple regression (e.g., one
voxel) is univariate and the matri-
ces from the general linear model
become vectors or scalars: Y → y,
X → x and B → b
y = xb + u,
where y is the dependent variable
(usually measured), x is the inde-
pendent variable (design variable)
and b is the parameter (regression
coefficient).
Finn Arup Nielsen 18 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Regression model
y
= b1
x1
+ b2
x2
+
u
Figure 12: Regression model. One voxel with 120 scans.Gray level indicate the value.
Regression model
y = b1x1 + b2x2 + u,
where y contains the values of
a specific voxels across scans.
x1 models, e.g., activation/rest
or patients/controls.
x2 models, e.g., the intercept,
— a constant value
u the noise/residual/error
Finn Arup Nielsen 19 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Categorical variables in design matrix
Categorical variable can be coded in two different ways:
‘Sigma-restricted’, where two groups (e.g., male and female) are coded
in one design variables, e.g., male +1 and female −1
x(1) =[
1, −1, 1, −1, 1, −1,]T
,
that leads to a design matrix with full rank.
‘Overparameterized’, where two groups are coded in two design variables
X(1:2) =
[
1 0 1 0 1 00 1 0 1 0 1
]T
,
that leads to a design matrix of degenerate rank.
(terminology from www.statsoftinc.com)
The overparameterized version is often preferred due to better ‘ordnung’.
Finn Arup Nielsen 20 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
ANCOVA — ANalysis of COVAriance
0 10 20 30 40 50 60 70 800
10
20
30
40
50
60
70
Age (covariate)
Figure 13: ANCOVA. Two groups (e.g., normals andpatients) with and age-effect. Normals/patients in-dicator variable (x1), age nuisance variable (x2) andintercept (x3).
1) Model with categorical and con-
tinuous design variables.
2) Conditions + Nuisances (covari-
ates, e.g., age)
An instance of multiple regression.
Why ANCOVA? Because the vari-
ance induced by the covariates
might make the test less powerful!
t-statistics for the example:
tordinary = −3.1 (1)
tANCOVA = −5.0 (2)
Finn Arup Nielsen 21 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Interactions
With ‘linear’ interactions (aka moderator effects)
y = x1b1 + x2b2 + (x1 ⊙ x2)b3 + +b4 + u,
where ⊙ is an elementwise multiplication: x3 = x1 ⊙ x2, e.g., for the first
scan: x1,3 = x1,1x1,2.
Finn Arup Nielsen 22 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Design matrix for paired t-test
1 2 3 4 5 6 7 8
2
4
6
8
10
12
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Figure 14: Design matrix X for paired t-test with 12scans, i.e., 6 pairs of scans. For each element blackindicates a one while white indicates a zero.
Paired t-test example
y =[
d1,2, d3,4, . . . , d11,12
]T,
where, e.g., d1,2 = y1 − y2
Degrees of freedom is lost com-
pared to the unpaired t-test.
New degrees of freedom:
r = N − rank(X)
= 12 − 7 = 5
Finn Arup Nielsen 23 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Estimation
Estimation requires only the but-
ton press of the user.
Finn Arup Nielsen 24 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Estimation of parameters
The ‘normal equation’ to estimate the parameters in the beta matrix
B(design variables× voxels)
B = (XTX)−1XTY,
or with the pseudo-inverse † (pinv in Matlab)
B = X†Y.
The pseudo-inverse will also work for design matrices of degenerate rank.
Each row in B is a volume.
In SPM the parameters are saved in files with the beta prefix.
Finn Arup Nielsen 25 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Estimation of error
The “fitted’ error matrix’ U (Mardia)
U = Y − XB.
The residual sum of squares and products (SSP) matrix UTU is a (voxels×voxels)-matrix.
In a mass-univariate test only the diagonal is used s(voxels × 1)
s = diag(UTU)
With degrees of freedom ν normalization
r = s/ν
In SPM the volume of residuals is saved in ResMS
Finn Arup Nielsen 26 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Statistical inference
The statistical inference entails
the specification of a so-called
‘contrast’ and the comparison of
the result of the contrast to a
statistical distribution.
Finn Arup Nielsen 27 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Example contrasts
Figure 15: SPM2 contrast manager.
Not all testable contrast are appro-
priate.
F -contrast for ANOVA with 3
groups encoded in an overparametrized
design matrix (cf. SPM2 spm conman.m)
C =
[
+1 −1 0 00 +1 −1 0
]
t-contrast with 2 groups, one co-
variate and one grand mean
C =[
+1 −1 0 0]
Finn Arup Nielsen 28 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
‘General Linear Hypothesis’
Hypothesis for a univariate t-test with the contrast vector c as a row
vector
H0 : cb = 0.
A univariate F -test with the constrast matrix C as a row vector
H0 : Cb = 0.
In SPM the values cB from a t-test are stored in volume files with con
prefix.
The t-test allows one to say something about the direction of the effect.
An F -test does not allow it.
Finn Arup Nielsen 29 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Hypothesis test example with t-test
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 10
10
20
30
40
50
60
70
80
90
Figure 16: Histogram of the lower tailarea of the t-value: 1 − p-value.
Matlab program with a random designmatrix and random image data:
X = rand(12, 5);Y = randn(size(X,1), 4000);
B = pinv(X) * Y;dof = size(X,1) - rank(X);U = Y - X*B;SSE = diag(U’*U)’;MSSE = SSE / dof;SE = sqrt(MSSE);
C = [ 1 -1 0 0 0 ];T = C*B ./ (SE * sqrt(C*pinv(X’*X)*C’));P = brede_cdf_t(T, dof);
figurehist(P, sqrt(length(P)));
Finn Arup Nielsen 30 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Multiple testing problem
Uncorrected
No p−values
Uncorrected+Corrected
Corrrected
Figure 17: Distribution of coordinates in the Brededatabase where the ‘uncorrected’ or ‘corrected’ P -values are given.
If 20.000 voxels are tested and a
statistical threshold on 0.05 is used
then around 1000 will be declared
active (significant) if the null hy-
pothesis is true: ‘uncorrected p-values’.
Usually this is dealt with by using
random field theory: ‘corrected p-values’.
Not always(!) according to the in-
formation in the Brede database.
If multiple contrasts are performed
this should also be corrected. This
is almost never done!
Finn Arup Nielsen 31 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Multiple testing corrections
Bonferroni correction
αBonferroni = α/N,
where N is the number of voxels, e.g., 0.05/20000 = 0.00000025
Random field theory
False discovery rate
Maximum statistics permutation testing
Finn Arup Nielsen 32 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Random field theory
Independent Gaussian noise
20 40 60 80 100 120
20
40
60
80
100
120
Smoothed with Gaussian kernel of FWHM 8 by 8 pixels
20 40 60 80 100 120
20
40
60
80
100
120
Smoothed image thresholded at Z > 2.75
20 40 60 80 100 120
20
40
60
80
100
120
0 1 2 3 4 50
5
10
15
20
25
30
Z score threshold
Exp
ecte
d E
C fo
r th
resh
olde
d im
age
Expected EC for smoothed image with 256 resels
Figure 18: Matthew Brett’s example. From (Brett, 1999b).
The ‘Euler characteris-
tics’ (EC) property counts
the number of blobs mi-
nus the number of holes
in a binary image
On high threshold there
are no holes, i.e., EC =
#blobs
On high threshold: The
expected EC ≈ P(EC =
1) = P(max > u)
Formulas for expected EC
exist for, e.g., Gaussian
random field.
Finn Arup Nielsen 33 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
False discovery rate
Signal + Gaussian white noise
−2
0
2
4
5% of null voxels are false +
P < 0.05 (uncorrected), Z > 1.6449
−2
0
2
4
5% of discoveries are false
P < 0.05 (FDR), Z > 3.014671
−2
0
2
4
5% probability of any false
P < 0.05 (Bonferroni), Z > 4.417173
−2
0
2
4
Figure 19: Multiple comparison corrections. Example by KeithWorsley (Worsley, 2004, figure 3).
False discovery rate (Gen-
ovese et al., 2002; Wors-
ley, 2004).
Find the largest k in or-
dered P -values: P1 ≤P2 ≤ . . . ≤ PN
Pk < αk/N.
P1 . . . Pk declared signifi-
cant.
Finn Arup Nielsen 34 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Maximum statistics permutation
Permutation (resampling without replacement) of the labels of the scans
(the interesting variables of the design matrix) (Holmes et al., 1996;
Nichols and Holmes, 2001).
Create a statistics, e.g., a ordinary t-statistcs
Take the maximum statistics across all voxels.
Iterate many times (several 1000 times) to generate a histogram of max-
imum values.
The multiple comparison problem can be accounted for — both over
voxels and contrasts. ‘Non-parametric’: No assumption of Gaussianity.
But the scans should be ‘exchangeable’ (not BOLD fMRI).
Finn Arup Nielsen 35 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Maximum statistics permutation
0 0.5 1 1.5 2 2.5
x 104
0
100
200
300
400
500
600Thermal pain
Fre
quen
cy
P=0.000
0 0.5 1 1.5 2 2.5
x 104
0
100
200
300
400Visual object recognition
Fre
quen
cy
Maximum statistics
P=0.029
Figure 20: Histogram of resampling distribution. The thickred lines indicate the maxima.
Example data set with 8 scans
with two states: ABABABAB.
Statistical parametric map:
t = (AAAA)− (BBBB)
Permutations
t1 = (ABAA) − (BBAB)
t2 = (BBAA) − (AABB)...
The P-values are the ratios of
max(tr) for r = 1 . . . R larger
than t
Finn Arup Nielsen 36 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Lyngby Toolbox
Figure 21: One of the windows in the Lyngby toolbox
Programmed by Matthew Lip-
trot, Lars Kai Hansen, Finn
Arup Nielsen, . . . (Hansen et al.,
1999)
Multivariate analyses: Clus-
ter analysis, canonical correla-
tion, independent component
analysis
Finn Arup Nielsen 37 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Brede Toolbox
Matlab toolbox with mul-
tivariate analysis, meta-
analytic modeling, visual-
izations, . . .
Graphical user interface for
partial correlation analysis,
suitable for data sets that
contain multiple variables
that should be tested, e.g.,
personality scores across
many regions. Includes
maximum statistics permu-
tation.
Finn Arup Nielsen 38 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
Brede database
Brede Database records Ta-
lairach/MNI coordinates from
experiments.
Online search from
http://hendrix.imm.dtu.dk
Example with online search on
two coordinates in left and right
amygdala in the experiments.
Finn Arup Nielsen 39 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
SPM plugins — third party software
Batch processing. Programs to construct batch jobs. Included in SPM5
with spm jobman.
INRIAlign. Robust motion alignment.
Diffusion. Functions for DWI MRI
Region of interest modeling (MarsBar, WFUPickAtlas),
Multivariate analysis (MM Toolbox),
‘Statistical Parametric Mapping Diagnosis’
Non-parametric permutation test (SnPM) (Holmes et al., 1996; Nichols
and Holmes, 2001)
. . .
Finn Arup Nielsen 40 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
MRIcro
MRIcro programmed by ChrisRorden for PC versions of Linux
and Microsoft Windows.
Slice view and volume renderingview. Overlay of functional im-ages on structural, drawing of re-gions and extraction of the brain
Includes a labeled volume (ALL)
based on lobar anatomy (Tzourio-Mazoyer et al., 2002), a la-beled volume (brodmann) based
on Brodmann areas, and a stan-dard high-resolution single sub-ject MR image with scull (ch2)and without scull (ch2bet)
Finn Arup Nielsen 41 February 8, 2008
Statistical Parametric Mapping (SPM) 2008
More information
SPM wiki, http://en.wikibooks.org/wiki/SPM and
http://en.wikipedia.org/wiki/Statistical parametric mapping
Email list, http://www.jiscmail.ac.uk/lists/SPM.html
Short Course on Statistical Parametric Mapping,
ftp://ftp.fil.ion.ucl.ac.uk/spm/course/notes04/slides/london2004.htm
‘Human Brain Function’ book. The methodological part is available on
the Internet, http://www.fil.ion.ucl.ac.uk/spm/doc/books/hbf2/
‘fMRI Neuroinformatics’ overview article (Nielsen et al., 2006).
Jonathan Taylors notes for his ‘stats191’ course: http://www-
stat.stanford.edu/˜jtaylo/courses/stats191/
Finn Arup Nielsen 42 February 8, 2008
References
References
Brett, M. (1999a). The MNI brain and the Talairach atlas. http://www.mrc-cbu.cam.ac.uk/Imaging/-mnispace.html. Accessed 2003 March 17.
Brett, M. (1999b). Thresholding with random field theory. http://www.mrc-cbu.cam.ac.uk/Imaging/Common/randomfields.shtml. Accessed 2005 March 3.
Friston, K. J., Holmes, A. P., Worsley, K. J., Poline, J.-B., Frith, C. D., and Frackowiak, R. S. J.(1995). Statistical parametric maps in functional imaging: A general linear approach. Human Brain
Mapping, 2(4):189–210. http://www.fil.ion.ucl.ac.uk/spm/papers/SPM 3/. A classic paper describingthe statistical model implemented in the SPM program.
Genovese, C. R., Lazar, N. A., and Nichols, T. (2002). Thresholding of statistical maps in functionalneuroimaging using the false discovery rate. NeuroImage, 15(4):870–878.
Hansen, L. K., Nielsen, F. A., Toft, P., Liptrot, M. G., Goutte, C., Strother, S. C., Lange, N.,Gade, A., Rottenberg, D. A., and Paulson, O. B. (1999). “lyngby” — a modeler’s Matlab tool-box for spatio-temporal analysis of functional neuroimages. In (Rosen et al., 1999), page S241.http://isp.imm.dtu.dk/publications/1999/hansen.hbm99.ps.gz. ISSN 1053–8119.
Holmes, A. P., Blair, R. C., Watson, J. D. G., and Ford, I. (1996). Nonparametric analysis of statisticimages from functional mapping experiments. Journal of Cerebral Blood Flow and Metabolism, 16(1):7–22. PMID: 8530558.
Kjems, U., Strother, S. C., Anderson, J. R., and Hansen, L. K. (1999a). Enhancing themultivariate signal of [15O] water PET studies with a new nonlinear neuroanatomical regis-tration algorithm. IEEE Transaction on Medical Imaging, 18(4):306–319. PMID: 10385288.http://www.imm.dtu.dk/pubdb/views/publication details.php?id=2837.
Kjems, U., Strother, S. C., Anderson, J. R., and Hansen, L. K. (1999b). A new unix toolbox fornon-linear warping of MR brain images applied to a [15O] water PET functional experiment. In (Rosenet al., 1999), page S18. ISSN 1053–8119.
Finn Arup Nielsen 43 February 8, 2008
References
Lancaster, J. L., Tordesillas-Gutierrez, D., Martinez, M., Salinas, F., Evans, A., K, K. Z., Mazziotta,J. C., and Fox, P. T. (2007). Bias between MNI and Talairach coordinates analyzed using the ICBM-152brain template. Human Brain Mapping, 28(11):1194–1205. PMID: 17266101. DOI: 10.1002/hbm.20345.Mardia, K. V., Kent, J. T., and Bibby, J. M. (1979). Multivariate Analysis. Probability and MathematicalStatistics. Academic Press, London. ISBN 0124712525.Nichols, T. E. and Holmes, A. P. (2001). Nonparametric permutation tests for functional neuroimag-ing experiments: A primer with examples. Human Brain Mapping, 15(1):1–25. PMID: 11747097.http://www3.interscience.wiley.com/cgi-bin/abstract/86010644/. ISSN 1065-9471. A reiteration of anolder permutation test article by Andrew Holmes. Lengthier and more accessible with three illustrativeexamples. An example shows that the permutation test with a pseudo-t statistics detects more “active”voxels than a parametric approach.Nielsen, F. A., Christensen, M. S., Madsen, K. H., Lund, T. E., and Hansen, L. K. (2006). fMRI neu-roinformatics. IEEE Engineering in Medicine and Biology Magazine, 25(2):112–119. PMID: 16568943.http://www2.imm.dtu.dk/pubdb/views/publication details.php?id=3516. An overview of some of thetools for and issues in fMRI neuroinformatics with description of, e.g., the SPM, AFNI and FSL pro-grams and the BrainMap, fMRIDC and Brede databases.Noll, D. C., Kinahan, P. E., Mintun, M. A., Thulborn, K. R., and Townsend, D. W. (1996). Comparisonof activation response using functional PET and MRI. NeuroImage, 3(3):S34. Second InternationalConference on Functional Mapping of the Human Brain.Rosen, B. R., Seitz, R. J., and Volkmann, J., editors (1999). Fifth International Conference on Functional
Mapping of the Human Brain, NeuroImage, volume 9. Academic Press.Talairach, J. and Tournoux, P. (1988). Co-planar Stereotaxic Atlas of the Human Brain. Thieme MedicalPublisher Inc, New York. ISBN 0865772932.Tzourio-Mazoyer, N., Landeau, B., Papathanassiou, D., Crivello, F., Etard, O., Delcroix, N., Ma-zoyer, B., and Joliot, M. (2002). Automated anatomical labeling of activations in SPM using amacroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage, 15(1):273–289.DOI: 10.1006/nimg.2001.0978.Worsley, K. J. (2004). Developments in random field theory. In Frackowiak, R. S. J.,Friston, K. J., Frith, C. D., Dolan, R. J., Price, C. J., Zeki, S., Ashburner, J., andPenny, W., editors, Human Brain Function. Elsevier, Amsterdam, Holland, second edition.http://www.fil.ion.ucl.ac.uk/spm/doc/books/hbf2/pdfs/Ch15.pdf.
Finn Arup Nielsen 44 February 8, 2008